The objectives of this proposal are to sequence the male-specific region of the Y chromosome (MSY) in chimpanzees using a clone-based iterative mapping and sequencing strategy and to fully analyze its sequence and structural organization. Detailed comparisons will be made to the recently completed human Y chromosome sequence, the first and only Y chromosome to be sequenced to date, shedding light on the structure, function, and evolution of this chromosome. This project also has biomedical implications, given the number and diversity of genes located on the Y chromosome. Because of the Y chromosome's rapid evolution, the human and chimpanzee Y chromosomes are structurally quite dissimilar. Therefore, valuable insights regarding the recent history of the Y chromosome and the extent to which large-scale rearrangements contributed to its present structure are likely to emerge from comparing the human Y sequence with that of the chimpanzee. In addition, striking phenotypic differences exist between humans and chimpanzees regarding male fertility and spermatogenesis, perhaps reflecting important species differences in Y-linked gene content. The recent announcement by the National Human Genome Research Institute prioritizing the chimpanzee as one of the next species on which to focus genome sequencing efforts emphasizes the scientific and medical significance of large-scale comparisons between the two species. However, because of several unique challenges posed by the Y chromosome, a dedicated effort will be required to obtain a complete and accurate sequence of this distinctive region of the chimpanzee genome.